在 HIV/HBV 合并感染患者中，接受替诺福韦为基础的抗逆转录病毒治疗长达 15 年期间，病毒持续复制和血清学应答：一项多中心前瞻性队列研究。

Persistent HBV replication and serological response during up to 15 years of tenofovir-based antiretroviral therapy in HIV/HBV-coinfected patients: a multicentre prospective cohort study.

机构信息

Sorbonne Université, INSERM, Institut Pierre Louis d'Épidémiologie et de Santé Publique, IPLESP, Paris F75012, France.

Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Service de Maladies Infectieuses et Tropicales, Lyon F69317, France.

出版信息

J Antimicrob Chemother. 2021 Oct 11;76(11):3009-3019. doi: 10.1093/jac/dkab294.

DOI:10.1093/jac/dkab294

PMID:34458919

Abstract

OBJECTIVES

To determine the extent of hepatitis B virus (HBV) suppression and its association with seroclearance of hepatitis 'e' antigen (HBeAg) and hepatitis B surface antigen (HBsAg) in HIV/HBV-coinfected patients undergoing long-term tenofovir-based antiretroviral therapy (ART).

METHODS

We prospectively followed 165 HIV/HBV-coinfected patients undergoing tenofovir-based ART. Serum HBV-DNA viral loads and HBeAg and HBsAg status were obtained at tenofovir initiation and every 6-12 months. We calculated the proportion achieving virological response (VR, <60 IU/mL) during follow-up. We also calculated rates of HBeAg- and HBsAg-seroclearance, which were compared between those who achieved versus never achieved VR during follow-up using an Exact binomial test.

RESULTS

During a median 8.1 years (IQR = 4.0-13.2) of tenofovir treatment, 152 (92.1%) patients were able to achieve VR and 13 (7.9%) never achieved VR (median HBV-DNA at the end of follow-up = 608 IU/mL, range = 67-52 400 000). The prevalence of individuals with detectable HBV-DNA (≥60 IU/mL) decreased during tenofovir treatment: 15.1% (n = 14/93) at 5 years, 3.2% (n = 2/62) at 10 years and, 3.2% (n = 1/31) at 15 years. 44/96 HBeAg-positive patients (6.15/100 person-years) had HBeAg-seroclearance and 13/165 patients overall (0.87/100 person-years) had HBsAg-seroclearance. No difference in HBeAg-seroclearance was observed between those who achieved versus never achieved VR (7.4 versus 3.7/100 person-years, P = 0.33), while HBsAg-seroclearance was only observed in those with VR (1.0 versus 0/100 person-years, P = 0.49; respectively). Individuals with VR also had a higher frequency of undetectable HIV-RNA during treatment (P < 0.001).

CONCLUSIONS

During long-term tenofovir-based ART for HIV/HBV coinfection, persistent HBV viraemia is apparent, but becomes less frequent over time. HBsAg-seroclearance only occurred in those with full HBV and relatively high HIV suppression.

摘要

目的

确定乙型肝炎病毒 (HBV) 抑制的程度及其与 HIV/HBV 合并感染患者长期接受替诺福韦为基础的抗逆转录病毒治疗 (ART) 时乙型肝炎 e 抗原 (HBeAg) 和乙型肝炎表面抗原 (HBsAg) 清除的关系。

方法

我们前瞻性地随访了 165 例接受替诺福韦为基础的 ART 的 HIV/HBV 合并感染患者。在替诺福韦治疗开始时和每 6-12 个月获得血清 HBV-DNA 病毒载量和 HBeAg 和 HBsAg 状态。我们计算了随访期间达到病毒学应答 (VR，<60IU/mL) 的比例。我们还计算了 HBeAg 和 HBsAg 清除率，并使用确切二项式检验比较了在随访期间达到和未达到 VR 的患者之间的清除率。

结果

在替诺福韦治疗的中位 8.1 年（IQR = 4.0-13.2）期间，152 例（92.1%）患者能够达到 VR，13 例（7.9%）从未达到 VR（中位随访结束时的 HBV-DNA 为 608IU/mL，范围为 67-5240000）。在替诺福韦治疗期间，检测到 HBV-DNA（≥60IU/mL）的个体比例下降：5 年内为 15.1%（n = 14/93），10 年内为 3.2%（n = 2/62），15 年内为 3.2%（n = 1/31）。44/96 例 HBeAg 阳性患者（6.15/100 人年）发生了 HBeAg 清除，165 例患者中共有 13 例（0.87/100 人年）发生了 HBsAg 清除。在达到和未达到 VR 的患者之间，HBeAg 清除率无差异（7.4 与 3.7/100 人年，P = 0.33），而 HBsAg 清除率仅见于达到 VR 的患者（1.0 与 0/100 人年，P = 0.49）。达到 VR 的患者在治疗期间也有更高的 HIV-RNA 无法检测到的频率（P < 0.001）。